tbuckley/cabot-search huggingface dataset:
Commentary
Authors: Saowanee Ngamruengphong, Yutaka Saito
Journal: Endoscopy (2023)

Local recurrence after piecemeal endoscopic mucosal resection (EMR) is common and it is a major drawback of this technique. Thermal ablation of resection margins after EMR using snare-tip soft coagulation has been shown to decrease the risk of local recurrence in a randomized trial [1]. Hybrid argon plasma coagulation (hAPC) is an alternative ablation technique that can be used to perform margin ablation. Recent studies on hAPC for post-EMR margin ablation showed low rates of local recurrence.
US Maternal Mortality Continues to Worsen
Authors: Emily Harris
Journal: JAMA (2023)

The US maternal mortality rate continued to increase in 2021, according to a new report from the National Center for Health Statistics.The trend predated the COVID-19 pandemic: between 2018 and 2019, the rate increased from 17.4 maternal deaths per 100 000 live births to 20.1.It then continued to rise to 23.8 in 2020 and to 32.9 in 2021.There were 1205 maternal deaths in 2021 compared with 658 in 2018.Disparities in maternal mortality also persisted in 2021, with 69.9 Black women dying per 100 000 live births-a 2.6 times higher rate than that of White women that year.For all racial and ethnic groups included in the analysis-Black, Hispanic, and White-the number of deaths per 100 000 live births increased every year from 2018 through 2021.The maternal mortality rate also increased substantially for women aged 40 years or older between 2020 to 2021, from about 107.9 deaths per 100 000 live births to 138.5.In 2019, the maternal mortality rate for this age group was 75.5, a decrease from 81.9 the year prior.
A proposal from the liver forum for the management of comorbidities in non-alcoholic steatohepatitis therapeutic trials
Authors: Raluca Pais, Bertrand Cariou, Mazen Noureddin, Sven Francque, Jörn M. Schattenberg, Manal F. Abdelmalek, Gadi Lalazar, Sharat Varma, Julie Dietrich, Veronica Miller, Arun Sanyal, Vlad Ratziu
Journal: Journal of Hepatology (2023)
Following the design path of isoform-selective Hsp90 inhibitors: Small differences, great opportunities
Authors: Jaka Dernovšek, Tihomir Tomašič
Journal: Pharmacology & Therapeutics (2023)

The heat shock protein 90 (Hsp90) family consists of four highly conserved isoforms: the mitochondrial TRAP-1, the endoplasmic reticulum-localised Grp94, and the cytoplasmic Hsp90α and Hsp90β. Since the late 1990s, this family has been extensively studied as a potential target for the treatment of cancer, neurological disorders, and infectious diseases. The initial approach was to develop non-selective, so-called pan-Hsp90 ATP-competitive inhibitors of the N-terminal domain. Many of these agents were tested in clinical trials, mainly for the treatment of cancer, but none of them succeeded in the clinic. This was mainly due to the lack of efficacy and various toxicities associated with the induction of heat shock response (HSR). This lack of success has prompted a turn to new approaches of Hsp90 inhibition. Thus, inhibitors selective for a particular isoform of Hsp90 have been developed. These isoform-selective inhibitors do not induce HSR and have a more targeted effect because not all client proteins are equally dependent on all four paralogues of Hsp90. However, it is extremely difficult to develop such selective compounds because the family is highly conserved. Hsp90α and Hsp90β have an amazing 95% identity of the N-terminal ATP binding site, differing only in two amino acid residues. Therefore, the focus of this review is to fully elucidate the key structural features of the selective inhibitor classes in terms of binding site dissimilarities. In addition to a methodological characterisation of the structure-activity relationships, the main advantages of selective inhibition of the TRAP-1, Grp94, Hsp90α and Hsp90β isoforms are discussed.
CRISPR screens identify gene targets at breast cancer risk loci
Authors: Natasha K. Tuano, Jonathan Beesley, Murray Manning, Wei Shi, Laura Perlaza-Jimenez, Luis F. Malaver-Ortega, Jacob M. Paynter, Debra Black, Andrew Civitarese, Karen McCue, Aaron Hatzipantelis, Kristine Hillman, Susanne Kaufmann, Haran Sivakumaran, Jose M. Polo, Roger R. Reddel, Vimla Band, Juliet D. French, Stacey L. Edwards, David R. Powell, Georgia Chenevix-Trench, Joseph Rosenbluh
Journal: Genome biology (2023)

Abstract Background Genome-wide association studies (GWAS) have identified &gt; 200 loci associated with breast cancer risk. The majority of candidate causal variants are in non-coding regions and likely modulate cancer risk by regulating gene expression. However, pinpointing the exact target of the association, and identifying the phenotype it mediates, is a major challenge in the interpretation and translation of GWAS. Results Here, we show that pooled CRISPR screens are highly effective at identifying GWAS target genes and defining the cancer phenotypes they mediate. Following CRISPR mediated gene activation or suppression, we measure proliferation in 2D, 3D, and in immune-deficient mice, as well as the effect on DNA repair. We perform 60 CRISPR screens and identify 20 genes predicted with high confidence to be GWAS targets that promote cancer by driving proliferation or modulating the DNA damage response in breast cells. We validate the regulation of a subset of these genes by breast cancer risk variants. Conclusions We demonstrate that phenotypic CRISPR screens can accurately pinpoint the gene target of a risk locus. In addition to defining gene targets of risk loci associated with increased breast cancer risk, we provide a platform for identifying gene targets and phenotypes mediated by risk variants.
Association of Body Surface Area With Access to Deceased Donor Liver Transplant and Novel Allocation Policies
Authors: Catherine E. Kling, Scott W. Biggins, Kiran M. Bambha, Lauren D. Feld, John H. Perkins, Jorge D. Reyes, James D. Perkins
Journal: JAMA Surgery (2023)

Importance Small waitlist candidates are significantly less likely than larger candidates to receive a liver transplant. Objective To investigate the magnitude of the size disparity and test potential policy solutions. Design, Setting, and Participants A decision analytical model was generated to match liver transplant donors to waitlist candidates based on predefined body surface area (BSA) ratio limits (donor BSA divided by recipient BSA). Participants included adult deceased liver transplant donors and waitlist candidates in the Organ Procurement and Transplantation Network database from June 18, 2013, to March 20, 2020. Data were analyzed from January 2021 to September 2021. Exposures Candidates were categorized into 6 groups according to BSA from smallest (group 1) to largest (group 6). Waitlist outcomes were examined. A match run was created for each donor under the current acuity circle liver allocation policy, and the proportion of candidates eligible for a liver based on BSA ratio was calculated. Novel allocation models were then tested. Main Outcomes and Measures Time on the waitlist, assigned Model for End-Stage Liver Disease (MELD) score, and proportion of patients undergoing a transplant were compared by BSA group. Modeling under the current allocation policies was used to determine baseline access to transplant by group. Simulation of novel allocation policies was performed to examine change in access. Results There were 41 341 donors (24 842 [60.1%] male and 16 499 [39.9%] female) and 84 201 waitlist candidates (53 724 [63.8%] male and 30 477 [36.2%] female) in the study. The median age of the donors was 42 years (IQR, 28-55) and waitlist candidates, 57 years (IQR, 50-63). Females were overrepresented in the 2 smallest BSA groups (7100 [84.0%] and 7922 [61.1%] in groups 1 and 2, respectively). For each increase in group number, waitlist time decreased (234 days [IQR, 48-700] for group 1 vs 179 days [IQR, 26-503] for group 6; P &amp;amp;lt; .001) and the proportion of the group undergoing transplant likewise improved (3890 [46%] in group 1 vs 4932 [57%] in group 6; P &amp;amp;lt; .001). The smallest 2 groups of candidates were disadvantaged under the current acuity circle allocation model, with 37% and 7.4% fewer livers allocated relative to their proportional representation on the waitlist. Allocation of the smallest 10% of donors (by BSA) to the smallest 15% of candidates overcame this disparity, as did performing split liver transplants. Conclusions and Relevance In this study, liver waitlist candidates with the smallest BSAs had a disadvantage due to size. Prioritizing allocation of smaller liver donors to smaller candidates may help overcome this disparity.
Patient Beliefs About Antibiotics for Appendicitis and Outcomes
Authors: Yong Yan, Yanhua Sha
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Association Between Acute Alcohol Use and Firearm-Involved Suicide in the United States
Authors: Shannon Lange, Huan Jiang, Mark S. Kaplan, Kawon Victoria Kim, Jürgen Rehm
Journal: JAMA Network Open (2023)

Importance Firearms are the method of suicide used most often in the US. Acute alcohol use is associated with an increased risk of suicide by firearm. However, the dose-response association between acute alcohol use and the probability of using a firearm as the method of suicide is unknown. Objective To evaluate the association between the amount of alcohol consumed and the probability of using a firearm as the method of suicide. Design, Setting, and Participants This cross-sectional study used mortality data from the US National Violent Death Reporting System on suicide decedents aged 18 years or older with a positive blood alcohol concentration (BAC; ie, ≥0.01 g/dL). Statistical analysis was performed from January 2003 to December 2020. Exposure Acute alcohol use, ascertained via postmortem toxicologic examination. Main Outcomes and Measures Probability of using a firearm as the method of suicide compared with all other methods of suicide. Results The study included 45 959 male suicide decedents (mean [SD] age, 42.6 [14.8] years) and 12 136 female suicide decedents (mean [SD] age, 44.2 [13.8] years) with a positive BAC; of those, 24 720 male decedents (53.8%) and 3599 female decedents (29.7%) used a firearm as the method of suicide. The probability of using a firearm as the method of suicide when alcohol is consumed was higher for male decedents, with the probability starting at just below 0.50 and increasing to approximately 0.75. In contrast, for female decedents, the probability began at just above 0.30 and increased to approximately 0.55. For both male and female decedents, the dose-response curves were an inverted U shape; as BAC increased, the probability of firearm-involved suicide initially increased and then decreased at very high BACs (approximately 0.40 g/dL for male decedents and approximately 0.30 g/dL for female decedents; these BACs were present among only a small percentage of alcohol-involved suicides: male decedents, 589 [1.3%]; female decedents, 754 [6.2%]). Conclusions and Relevance This cross-sectional study of suicide decedents who had consumed alcohol prior to their death suggests that, as alcohol consumption increased, the probability of a firearm-involved suicide increased until a certain BAC, at which point the probability started to decrease.
More Attention Should Be Paid to Less Severe Nonculprit Lesions—Reply
Authors: Shamir R. Mehta, Natalia Pinilla-Echeverri, John A. Cairns
Journal: JAMA Cardiology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Overcoming Implementation Challenges With Innovation and Patient Empowerment—Let’s Keep Moving With Prehabilitation
Authors: Kathryn N. Porter Starr, Juliessa M. Pavon, Sandhya A. Lagoo-Deenadayalan
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Artificial Pancreas Improved Outcomes in Children With Type 1 Diabetes
Authors: Emily Harris
Journal: JAMA (2023)

The US maternal mortality rate continued to increase in 2021, according to a new report from the National Center for Health Statistics.The trend predated the COVID-19 pandemic: between 2018 and 2019, the rate increased from 17.4 maternal deaths per 100 000 live births to 20.1.It then continued to rise to 23.8 in 2020 and to 32.9 in 2021.There were 1205 maternal deaths in 2021 compared with 658 in 2018.Disparities in maternal mortality also persisted in 2021, with 69.9 Black women dying per 100 000 live births-a 2.6 times higher rate than that of White women that year.For all racial and ethnic groups included in the analysis-Black, Hispanic, and White-the number of deaths per 100 000 live births increased every year from 2018 through 2021.The maternal mortality rate also increased substantially for women aged 40 years or older between 2020 to 2021, from about 107.9 deaths per 100 000 live births to 138.5.In 2019, the maternal mortality rate for this age group was 75.5, a decrease from 81.9 the year prior.
Arresting microbiome development limits immune system maturation and resistance to infection in mice
Authors: Jean-Bernard Lubin, Jamal Green, Sarah Maddux, Lidiya Denu, Tereza Duranova, Matthew Lanza, Meghan Wynosky-Dolfi, Julia N. Flores, Logan P. Grimes, Igor E. Brodsky, Paul J. Planet, Michael A. Silverman
Journal: Cell Host & Microbe (2023)
Widespread Clean Cooking Fuel Scale-Up and under-5 Lower Respiratory Infection Mortality: An Ecological Analysis in Ecuador, 1990–2019
Authors: Carlos F. Gould, M. Lorena Bejarano, Marianthi-Anna Kioumourtzoglou, Alison G. Lee, Ajay Pillarisetti, Samuel B. Schlesinger, Enrique Terán, Alfredo Valarezo, Darby W. Jack
Journal: Environmental Health Perspectives (2023)

Background: Nationwide household transitions to the use of clean-burning cooking fuels are a promising pathway to reducing under-5 lower respiratory infection (LRI) mortality, the leading cause of child mortality globally, but such transitions are rare and evidence supporting an association between increased clean fuel use and improved health is limited. Objectives: This study aimed to investigate the association between increased primary clean cooking fuel use and under-5 LRI mortality in Ecuador between 1990 and 2019. Methods: We documented cooking fuel use and cause-coded child mortalities at the canton (county) level in Ecuador from 1990 to 2019 (in four periods, 1988–1992, 1999–2003, 2008–2012, and 2015–2019). We characterized the association between clean fuel use and the rate of under-5 LRI mortalities at the canton level using quasi-Poisson generalized linear and generalized additive models, accounting for potential confounding variables that characterize wealth, urbanization, and child health care and vaccination rates, as well as canton and period fixed effects. We estimated averted under-5 LRI mortalities accrued over 30 y by predicting a counterfactual count of canton-period under-5 LRI mortalities were clean fuel use to not have increased and comparing with predicted canton-period under-5 LRI mortalities from our model and observed data. Results: From 1990 to 2019, the proportion of households primarily using a clean cooking fuel increased from 59% to 95%, and under-5 LRI mortality fell from 28 to 7 per 100,000 under-5 population. Canton-level clean fuel use was negatively associated with under-5 LRI mortalities in linear and nonlinear models. The nonlinear association suggested a threshold at approximately 60% clean fuel use, above which there was a negative association. Increases in clean fuel use between 1990 and 2019 were associated with an estimated 7,300 averted under-5 LRI mortalities (95% confidence interval: 2,600, 12,100), accounting for nearly 20% of the declines in under-5 LRI mortality observed in Ecuador over the study period. Discussion: Our findings suggest that the widespread household transition from using biomass to clean-burning fuels for cooking reduced under-5 LRI mortalities in Ecuador over the last 30 y. https://doi.org/10.1289/EHP11016
Characterization of the rotavirus assembly pathway in situ using cryoelectron tomography
Authors: Pranav N.M. Shah, James B. Gilchrist, Björn O. Forsberg, Alister Burt, Andrew Howe, Shyamal Mosalaganti, William Wan, Julika Radecke, Yuriy Chaban, Geoff Sutton, David I. Stuart, Mark Boyce
Journal: Cell Host & Microbe (2023)

Rotavirus assembly is a complex process that involves the stepwise acquisition of protein layers in distinct intracellular locations to form the fully assembled particle. Understanding and visualization of the assembly process has been hampered by the inaccessibility of unstable intermediates. We characterize the assembly pathway of group A rotaviruses observed in situ within cryo-preserved infected cells through the use of cryoelectron tomography of cellular lamellae. Our findings demonstrate that the viral polymerase VP1 recruits viral genomes during particle assembly, as revealed by infecting with a conditionally lethal mutant. Additionally, pharmacological inhibition to arrest the transiently enveloped stage uncovered a unique conformation of the VP4 spike. Subtomogram averaging provided atomic models of four intermediate states, including a pre-packaging single-layered intermediate, the double-layered particle, the transiently enveloped double-layered particle, and the fully assembled triple-layered virus particle. In summary, these complementary approaches enable us to elucidate the discrete steps involved in forming an intracellular rotavirus particle.
Selective Decontamination of the Digestive Tract and Hospital Mortality in Critically Ill Patients Receiving Mechanical Ventilation
Authors: Nicolas Massart, Pierre Fillatre, Christophe Camus
Journal: JAMA (2023)

To the Editor The recently published SuDDICU randomized clinical trial1 confirmed a clinically relevant yet nonsignificant mortality reduction in mechanically ventilated critically ill patients receiving selective digestive decontamination (SDD). We have some comments about this study.1
Selective Decontamination of the Digestive Tract and Hospital Mortality in Critically Ill Patients Receiving Mechanical Ventilation—Reply
Authors: John A. Myburgh, Ian M. Seppelt, Simon R. Finfer
Journal: JAMA (2023)

In Reply The SuDDICU trial1 was designed to determine whether the administration of SDD as a preventive infection control strategy improved patient-centered outcomes, specifically hospital mortality, in intensive care unit patients receiving mechanical ventilation.
Neighborhood environmental vulnerability and pediatric asthma morbidity in US metropolitan areas
Authors: Sneha Kannoth, Sarah E. Chung, Kelvin D. Tamakloe, Sandra S. Albrecht, Alexander Azan, Earle C. Chambers, Perry E. Sheffield, Azure Thompson, Jennifer A. Woo Baidal, Stephanie Lovinsky-Desir, Jeanette A. Stingone
Journal: Journal of Allergy and Clinical Immunology (2023)
Trends in Dietary Vitamin A Intake Among US Adults by Race and Ethnicity, 2003-2018
Authors: Ting-Yuan David Cheng, Carrollyn Ferderber, Benjamin Kinder, Yu-Jung Jenny Wei
Journal: JAMA (2023)

This study uses data from the 2003-2004 to 2017-2018 National Health and Nutrition Examination Surveys (NHANES) to assess whether a difference exists in dietary vitamin A intake as a marker of consumption of vitamin A–rich foods among Black, Hispanic, and White adults in the US.